Use of low molecular weight amino alcohols in ophthalmic compositions

ABSTRACT

The use of low molecular weight amino alcohols in ophthalmic boric solution is described herein. These compounds have been found to enhance the efficacy of antimicrobial preservatives. Particularly preferred amino alcohols are 2-amino-2-methyl-1-propanol (AMP), 2-dimethylamino-2-methyl-1-propanediol (DMAMP), 2-amino-2-ethylpropanol (AMP), 2-amino-2-methyl-1,3-propanediol (AMPD), and 2-amino-1-butanol (AB). The ophthalmic compositions further optionally comprise a borate/polyol buffer system and an alkylamine.

This appln. is a 371 of PCT/US97/20826 filed Nov. 17, 1997 and claimsbenefit of Prov. No. 60/033,079 filed Dec. 13, 1996.

BACKGROUND OF THE INVENTION

The present invention relates to the field of ophthalmology. Morespecifically, the invention relates to the use of low molecular weightamino alcohols in products for treating contact lenses, as well as otherophthalmic products. The amino alcohols described herein have been foundto be useful in preserving ophthalmic compositions. The amino alcoholshave also been found to be useful in enhancing the activity ofanti-microbial preservatives, and have been found to be particularlyeffective when combined with borate or borate/polyol buffer systems.

Ophthalmic compositions generally must include an anti-microbial agentto prevent contamination of the compositions by bacteria, fungi andother microbes. Such compositions may come into contact with the corneaeither directly or indirectly. The cornea is particularly sensitive toexogenous chemical agents. Consequently, in order to minimize thepotential for harmful effects on the cornea, it is necessary to useanti-microbial agents which are relatively non-toxic to the cornea, andto use such agents at the lowest possible concentrations (i.e., theminimum amounts required in order to perform their anti-microbialfunctions). This balancing of the anti-microbial efficacy and potentialtoxicological activity of anti-microbial agents is sometimes difficultto achieve. More specifically, the anti-microbial agent concentrationnecessary for useful preservation of ophthalmic formation ordisinfection of contact lenses may create the potential fortoxicological effects on the cornea and/or other ophthalmic tissues.Using lower concentrations of the anti-microbial agents generally helpsto reduce the potential for such toxicological effects, but the lowerconcentrations may be less effective for biocidal efficacy of ophthalmiccompositions. This weaker activity may create the potential formicrobial contamination of the compositions and ophthalmic infectionsresulting from such contaminations. This is also a serious problem,since ophthalmic infections involving pseudomonas aeruginosa or othervirulent microorganisms can lead to loss of visual function or even lossof the eye. Thus, there is a need for a means of enhancing the activityof anti-microbial agents so that very low concentrations of these agentscan be utilized without increasing the potential for toxicologicaleffects or increasing the risk of microbial contamination and resultingophthalmic infections.

Numerous anti-microbial agents have been used or suggested in the artfor preserving ophthalmic compositions or disinfecting contact lenses.Such agents have included: benzalkonium chloride (BAC), thimerosal,chlorhexidine, polymeric biguanides, such as polyhexylmethyl biguanides(PHMB), and polymeric quaternary ammonium agents, such aspolyquaternium-1. Other agents have included alkylamines, such as theamidoamines described in U.S. Pat. Nos. 5,393,491 (Dassanayake et al.)and 5,573,776 (Dassanayake et al.). While all of these agents haveoffered some level of utility, their use has also led to certainlimitations or drawbacks. For example, thimerosal, which containsmercury, has caused severe ocular irritation resulting from contact lensdisinfecting; BAC tends to complex in a detrimental way with negativeionic species typical in ophthalmic compositions and the polymericbiguanides and quaternary ammonium agents, although less ophthalmicallyirritating/toxic, have limited anti-microbial efficacy against certainspecies of fungi, including Aspergillus fumigatus and Aspergillus niger.Furthermore, new FDA disinfecting requirements are now being implementedwhich require even a greater magnitude of microbial kill against agreater number of microorganisms. Thus, a need exists for enhancing theeffectiveness of these otherwise useful anti-microbial agents.

Compositions for treating contact lenses and other types of ophthalmiccompositions are generally formulated as isotonic, buffered solutions.One approach to enhancing the anti-microbial activity of suchcompositions is to include multi-functional components in thecompositions. In addition to performing their primary functions, such ascleaning or wetting contact lens surfaces (e.g., surfactants), bufferingthe compositions (e.g., borate), or chelating undesirable ions (e.g.,EDTA), these multi-functional components also serve to enhance theoverall anti-microbial activity of the compositions. For example,ethylenediaminetetraacetic acid and the monosodium, disodium andtrisodium salts thereof (collectively referred to herein as “EDTA”) hasbeen widely used for many years in ophthalmic products, particularlyproducts for treating contact lenses. It has been used in such productsfor various purposes, but particularly for its supplementalanti-microbial activity and as a chelating agent The inclusion of EDTAin contact lens care products and other ophthalmic compositions enhancesthe anti-microbial efficacy of chemical preservatives contained in suchcompositions, particularly the efficacy of those preservatives againstgram negative bacteria.

Borate buffer systems are used in various types of ophthalmiccompositions. For example, two commercial solutions for disinfectingcontact lenses, OPTI-SOFT® (0.001% polyquaternium-1) DisinfectingSolution marketed by Alcon Laboratories, Inc. and ReNu® Multi-PurposeSolution (0.00005% polyhexamethylene biguanide) marketed by Bausch &Lomb, Inc., contain borate buffer systems which contribute to thedisinfecting efficacy of the solutions. An improved borate buffer systemfor ophthalmic compositions is described in U.S. Pat. Nos. 5,342,620(Chowhan) and 5,505,953 (Chowhan). That system utilizes borate incombination with one or more polyols, such as mannitol. This combinationenhances the anti-microbial activity of compositions, beyond theenhancement obtained with borate alone. However, the present inventorshave found that the water soluble complex formed by the borate/polyolalso reduces the pH of compositions significantly. As a result ofefforts directed to solving this and other problems, the presentinventors have discovered that certain amino alcohols can be effectivelyand safely utilized to provide pH-buffering of ophthalmic compositionsand to further enhance the anti-microbial activity of the compositions.

The use of tromethamine in compositions and methods for disinfectingcontact lenses is described in U.S. Pat. No. 5,422,073 (Mowrey-McKee, etal.). This publication indicates that a synergistic effect is obtainedwhen tromethamine is combined with other known microbicides andchelating agents. EDTA is identified as the preferred chelating agent.

In view of the foregoing, there is a need for an improved means forenhancing the activity of anti-microbial agents so as to preserveophthalmic compositions from microbial contamination and disinfectcontact lenses more efficaciously. The present invention is directed tosatisfying this need.

SUMMARY OF THE INVENTION

The present invention is based on a new use of a specific group of lowmolecular weight amino alcohols. The present inventors have found thatthe amino alcohols described herein enhance the activity ofanti-microbial agents, particularly when utilized in combination withborate or borate/polyol buffer systems. The enhancement is more thanadditive. Thus, although the mechanisms of action are not fullyunderstood, it is believed that the low molecular weight amino alcoholsof the present invention produce a synergistic enhancement ofanti-microbial activity.

The present inventors have also found that the subject amino alcoholsare very effective in neutralizing the acid pH of borate/polyolcomplexes. This buffering effect of the amino alcohols is significant.Although conventional bases, such as sodium hydroxide, may be utilizedto adjust the pH of acidic solutions containing borate/polyol complexes,the amino alcohols described herein have a significantly higherbuffering capacity. This enhanced buffering capacity is particularlyimportant if the compositions contain anti-microbial agents which are pHdependent (e.g., alkyl amidoamines). If the pH of such compositions isnot maintained within the range required for maximum anti-microbialactivity, the overall anti-microbial activity of the composition may bereduced. The use of borate-polyol buffering system may alsosignificantly reduce the amount of NaOH necessary for pH adjustments,and therefore reduce the amount of ions in the compositions. Thisfeature is particularly significant when ion sensitive anti-microbialagents, such as polyquaternium-1, are employed.

The amino alcohols may be used in various types of ophthalmiccompositions, particularly compositions for treating contact lenses,such as disinfectants, cleaners, comfort drops and rewetting drops. Thelow molecular weight amino alcohols are particularly useful incompositions for disinfecting, rinsing, storing and/or cleaning contactlenses. When these compounds are combined with borate buffer systems,the combination also helps to preserve the products against microbialcontamination. This anti-microbial effect of the amino alcohol/boratecombination reduces the amount of anti-microbial agent required forpreservative purposes, and in some instances, may totally eliminate theneed for a conventional anti-microbial preservative agent.

The present invention is particularly directed to the provision ofimproved compositions for disinfecting contact lenses. The compositionshave significantly enhanced anti-microbial activity, relative to priorcompositions containing the same primary disinfecting agents (e.g.,polyquaternium-1). The enhancement is achieved by means of a combinationof formulation criteria, including the use of a borate/polyol complexand one or more amino alcohols, as described herein. This enhancement ofanti-microbial activity is highly significant. Preferred disinfectingcompositions also contain a relatively small amount of an alkylamine.New government regulations in some countries have, in effect, created aneed for compositions having significantly greater anti-microbialactivity. More specifically, the new regulations require thatcompositions for disinfecting contact lenses be capable of achievingdisinfection without assistance from other compositions (e.g., cleaningcompositions or preserved saline rinsing solutions). The enhancement ofanti-microbial activity achieved by means of the present inventionenables contact lens disinfecting compositions to satisfy this standard.

DETAILED DESCRIPTION OF THE INVENTION

The low molecular weight amino alcohols which may be utilized in thepresent invention are water soluble and have a molecular weight in therange of from about 60 to about 200 grams/mole. The following compoundsare representative of the low molecular weight amino alcohols which maybe utilized in the present invention: 2-Amino-2-methyl-1-propanol (AMP),2-dimethylamino-methyl-1-propanediol (DMAMP),2-amino-2-ethyl-1,3-propanediol (AEPD), 2-amino-2-methyl-1,3-propanediol(AMPD), 2-amino-1-butanol (AB). “AMP-95,” which refers to 95% pure AMPand 5% water, is the most preferred low molecular weight amino alcoholof the present invention. These amino alcohols are availablecommercially from Angus Chemical Company (Buffalo Grove, Ill.).

The amount of amino alcohol used will depend on the molecular weight ofthe amino alcohol selected, the other ingredients in the composition,i.e., other anti-microbial agents, chelating agents, buffering agents,tonicity agents, and the function of the anti-microbial agents containedin the ophthalmic compositions (i.e., preservation of compositions ordisinfection of contact lenses). In general, one or more of theabove-described amino alcohols will be utilized in a concentration offrom about 0.01 to about 2.0 percent by weight/volume (“%w/v”), andpreferably from 0.1 to 1.0%w/v. When borate/polyol complexes areemployed with the amino alcohol compositions of the present invention,the amino alcohols will generally be present in an amount necessary toneutralize the pH of the complex, or bring the composition to a desiredpH. This amount, therefore, is a function of the particularborate/polyol mixture and concentration.

The low molecular weight amino alcohols described herein may be includedin various types of ophthalmic compositions to enhance anti-microbialactivity, or for the other purposes mentioned above. Examples of suchcompositions include: ophthalmic pharmaceutical compositions, such astopical compositions used in the treatment of glaucoma, infections,allergies or inflammation; compositions for treating contact lenses,such as cleaning products and products for enhancing the ocular comfortof patients wearing contact lenses; and various other types ofcompositions, such as ocular lubricating products, artificial tears,astringents, and so on. The compositions may be aqueous or non-aqueous,but will generally be aqueous.

In addition to the low molecular weight amino alcohols described above,the compositions of the present invention may contain one or moreanti-microbial agents to preserve the compositions from microbialcontamination and/or disinfect contact lenses. For example, thecompositions may contain the anti-microbial agent known aspolyquatemium-1 or POLYQUAD® (registered trademark of AlconLaboratories, Inc.); the use of this agent as a preservative inophthalmic compositions is described in U.S. Pat. No. 4,525,346 (Stark).The entire contents of the Stark '346 patent are hereby incorporated inthe present specification by reference. Additional examples ofanti-microbial agents include chlorhexidine, alexidine, hexetidine,polyhexamethylene biguanide, benzalkonium chloride, benzododecinumbromide, alkylamines, alkyl di-, tri-amine and other anti-microbialagents utilized as anti-microbial preservatives or disinfecting agentsin ophthalmic compositions. The inclusion of one or more of theabove-described low molecular weight amino alcohols in ophthalmiccompositions containing such anti-microbial agents enhances the overallanti-microbial activity of the compositions. This enhancement isparticularly evident when the compositions include a borate orborate-polyol buffer system.

As indicated above, the low molecular weight amino alcohols describedabove are preferably used in combination with borate or borate/polyolbuffer systems. As used herein, the term borate shall refer to boricacid, salts of boric acid and other pharmaceutically acceptable borates,or combinations thereof The following borates are particularlypreferred: boric acid, sodium borate, potassium borate, calcium borate,magnesium borate, manganese borate, and other such borate salts. As usedherein, and unless otherwise indicated, the term polyol shall refer toany compound having at least two adjacent —OH groups which are not intrans configuration relative to each other. The polyols can be linear orcyclic, substituted or unsubstituted, or mixtures thereof, so long asthe resultant complex is water soluble and pharmaceutically acceptable.Examples of such compounds include: sugars, sugar alcohols, sugar acidsand uronic acids. Preferred polyols are sugars, sugar alcohols and sugaracids, including, but not limited to: mannitol, glycerin, xylital andsorbitol. Especially preferred polyols are mannitol and sorbitol; mostpreferred is sorbitol. The use of borate-polyol complexes in ophthalmiccompositions is described in commonly assigned U.S. Pat. Nos. 5,342,620(Chowhan) and 5,505,953 (Chowhan); the entire contents of which arehereby incorporated in the present specification by reference. Thecompositions of the present invention preferably contain one or moreborates in an amount of from about 0.01 to about 2.0% w/v, morepreferably from about 0.3 to 1.2% w/v, and one or more polyols in anamount of from about 0.01 to 5.0% w/v, more preferably from about 0.6 to2.0% w/v.

As stated above, current disinfecting compositions are unable to meetthe new FDA requirements for disinfecting efficacy of contact lensdisinfecting compositions. The compositions of the present inventionimprove on these prior art compositions with the inclusion of aminoalcohols in the compositions. The most preferred contact lensdisinfecting compositions of the present invention comprise one or morelow molecular weight amino alcohol(s), a borate-polyol buffer, ananti-microbial agent, as described above, and an alkylamine.

Alkylamines have been described in commonly owned U.S. Pat. Nos.5,393,491 (Dassanayake et al.), and 5,573,726 (Dassanayake et al.), andU.S. patent application Ser. No. 08/381,889. The foregoing patents andpatent application are hereby incorporated in the present specificationby reference. These alkylamines possess both anti-bacterial andanti-fungal activity. Preferred alkylamines are the amidoamines, asdescribed in the above-referenced Dassanayake et al. patents. The mostpreferred amidoamine is myristamidopropyldimethyl-amine (“MAPDA”).

The amount of alkylamine in the compositions of the present inventionwill vary, due to various factors such as: anti-microbial potency andpotential toxicity of the particular alkylamine. The present inventorshave found, however, that the amount of alkylamines, particularly theamidoamines, useful in the compositions of the present invention isdramatically lower when combined with compositions comprising boratebuffers, than when the alkylamines are employed without borates.Generally, the alkylamines will be present in concentrations of fromabout 0.00005 to about 0.01% w/v, when combined with borates.

As will be appreciated by those skilled in the art, the preserving ordisinfecting compositions may also contain a wide variety of otheringredients, such as tonicity agents (e.g., sodium chloride ormannitol), surfactants (e.g., alkyl ethoxylates andpolyoxyethylene/polyoxypropylene copolymers), and viscosity adjustingagents. The present invention is not limited with respect to the typesof ophthalmic compositions in which the other low molecular weight aminoalcohols described above are utilized.

All of the above-described compositions will be formulated so as to becompatible with the eye and/or contact lenses to be treated with thecompositions. As will be appreciated by those skilled in the art, theophthalmic compositions intended for direct application to the eye willbe formulated so as to have a pH and tonicity which are compatible withthe eye. This will normally require a buffer to maintain the pH of thecomposition at or near physiologic pH (i.e., 7.4) and may require atonicity agent to bring the osmolality of the composition to a level ator near 210-320 milliosmoles per kilogram (mOsm/kg). The formulation ofcompositions for disinfecting and/or cleaning contact lenses willinvolve similar considerations, as well as considerations relating tothe physical effect of the compositions on contact lens materials andthe potential for binding or absorption of the components of thecomposition by the lens.

The following examples are presented to further illustrate selectedembodiments of the present invention.

EXAMPLE 1

The following saline solutions containing various amino alcohols at aconcentration of 1.2% were prepared for comparative purposes. Thecomposition of the solutions is presented below. The pH of the solutionswas adjusted to 7.4 with hydrochloric acid. The amino alcohols consistedof 2-Amino-2-methyl-1-propanol (AMP),2-dimethylamino-methyl-1-propanediol (DMAMP),2-amino-2-ethyl-1,3-propanediol (AEPD), 2-amino-2-methyl-1,3-propanediol(AMPD), and 1,4-Bis(2-hydroxyethyl)-piperazine (BHP). The osmolalitiesof the solutions were 335, 250, 254, 304 and 208 mOsm/kg, respectively.ingredients Amount (w/v%)

Ingredients Amount (w/v %) Amino Alcohol 1.2% Sodium Chloride 0.3%Disodium Edetate 0.05% Purified Water QS

The antibacterial activity of the above-escribed saline solutionsagainst S. marcescens was evaluated. The formulations were evaluated byinoculating 20 ml of each solution with 0.1 ml of a microbialsuspension. The final concentration was 10⁶ colony forming units(“CFUs”) per ml. At each time point, pour plates of SCDA were preparedcontaining diluted aliquots of the various test samples. The bacteriaand yeast plates were incubated at 30° to 35° C. for 2 to 3 days. Themold plates were incubated at 20° to 25° C. for five days. Following thecolony incubation period, the number of CFUs were counted and the logreduction of the CFUs relative to the starting amount was calculated.

The results at 6 and 24 hours (in log reduction of survivors) are shownin Table 1 below:

TABLE 1 Log Reduction of Survivors Amino Alcohol 6 hours 24 hours AMP0.1 0.5 DMAMP 0.0 0.7 AEPD 0.0 0.7 AMPD 0.0 0.0 BHP 0.1 0.1

As indicated by the foregoing data, all of the formulations exhibitedminimal activity against S. marcescens.

EXAMPLE 2

The following is an example of a preserving composition of the presentinvention (Formulation A) and a comparative composition (Formulation B).Both formulations, contain a borate/polyol buffer system (i.e., boricacid and mannitol), but differ in that Formulation A utilizes AMP-95 andFormulation B utilizes NaOH to adjust the pH. The formulations wereprepared by first sequentially dissolving in 90 ml of purified water,boric acid, mannitol, poloxamine and disodium edetate. AMP-95 was addedto Formulation A and the volume was adjusted to 100 ml with purifiedwater. The pH of Formulation A was 7.4. The pH of Formulation B wasadjusted to 7.4 with 6N NaOH, and the volume of the solution wasadjusted to 100 ml with purified water. Both formulations had anosmolality of about 200 mOsm/kg.

The compositions of the two formulations are set forth below:

Amount (w/v %) Ingredients Formulation A Formulation B Boric Acid 1.0%1.0% Mannitol 1.5% 1.5% Disodium Edetate 0.05% 0.05% Polaxamine 0.1%0.1% AMP-95 0.56% — Sodium hydroxide — pH to 7.4 Purifled Water QS QS

The anti-microbial activity of the formulations against S. marcescensand P. aeruginosa was evaluated. A similar microbial protocol to theExample 1 protocol was employed The results are presented in Table 2below:

TABLE 2 Microorganism Time Formulation A Formulation B S. marcescens 6hours 0.1 0.0 24 hours 1.1 0.2 168 hours 4.5 1.5 P. aeruginosa 6 hours5.0 1.0 24 hours 6.0 1.4 Note: Underline numbers represent no survivors.

As indicated by the foregoing data, Formulation A exhibitedsignificantly greater antibacterial activity than Formulation B, whichdoes not contain an amino alcohol in accordance with the presentinvention. This example demonstrates that the effect of amino alcohol ina borate composition surpasses the anti-bacterial effect of EDTA alone(Formulation B).

EXAMPLE 3

The following is a comparative example of a preserving and/ordisinfecting composition of the present invention (Formulation C) and acomparative composition (Formulation D). Two formulations similar tothose described in Example 2 above, but containing the anti-microbialagent POLYQUAD®, were prepared. The formulations were prepared by meansof procedures similar to those described in Example 2, above. POLYQUAD®was added before final pH adjustment. The pH of formulation C was 7.4;the pH of Formulation D was adjusted to pH 7.4 with 6N NaOH. Thecomposition of the formulations is presented below:

Amount (w/v %) Ingredients Formulation C Formulation D Boric Acid 1.0%1.0% Mannitol 1.5% 1.5% Disodium Edetate 0.05% 0.05% Polaxamine 0.1%0.1% POLYQUAD ® 0.0005% 0.0005% AMP-95 0.56% — Sodium Hydroxide — pH to7.4 Purified Water QS QS

The anti-microbial activity of the formulations against S. marcescens,S. aureus and P. aeruginosa was evaluated. Microbial protocols similarto the Example 1 protocol were employed. The results are presented inTable 3 below:

TABLE 3 Microorganism Time Formulation C Formulation D S. marcescens 6hours 2.9 2.4 24 hours 3.3 3.0 168 hours 6.1  4.8 S. aureus 6 hours 5.14.4 24 hours 6.1  5.9 P. aeruginosa 6 hours 6.0  5.3 24 hours 6.0  6.0 Note: the underline numbers represent no survivors.

These results demonstrate that the amino alcohol contained inFormulation C significantly enhanced the anti-microbial activity of thecomposition.

EXAMPLE 4

The following is a preferred multi-purpose composition for the cleaning,disinfecting, rinsing and storing of soft hydrophilic lenses:

Ingredient % (w/v) Polyquaternium-1 0.001 Boric acid 0.6  Sorbitol 1.2 Sodium chloride 0.1  Sodium citrate 0.65  Tetronic 1304 0.05  DisodiumEdetate 0.05  Sodium hydroxide pH 7.8   Hydrochloric acid pH 7.8  Purified water QS AMP-95 0.45% MAPDA  0.0005%

The anti-microbial activity of the above composition against A.fumigatus, C. albicans, F. solani, P. aeruginosa, S. marcescens, S.aureus and S. warneri was evaluated. Microbial protocols similar to thatof Example 1 for the various microorganisms were employed. The resultsare illustrated in Table 4, below:

TABLE 4 Microorganism Time (Hrs) Log Reduction A. fumigatus 4 2.2 ATCC10894 6 3.1 24 4.8 48 4.8 C. albicans 4 1.5 ATCC 10231 6 1.7 24 2.7 484.0 F. solani 4 3.8 ATCC 36031 6 4.3 24 5.6 48 5.8 P. aeruginosa 4 4.7ATCC 9027 6 5.7 24 6.1 48 6.1 S. marcescens 4 3.3 ATCC 13880 6 4.1 246.0 48 4.7 S. marcescens 4 2.1 ATCC 14041 6 2.7 24 5.6 48 5.6 S. aureus4 3.7 ATCC 6538 6 3.7 24 5.5 48 6.1 S. warneri 4 4.9 ATCC 17917 6 5.1 245.9 48 5.9

EXAMPLE 5

The following is a comparative example of a multi-purpose composition ofthe present invention (Formulation E) and a comparative composition(Formulation F). The two formulations are the same, except thatFormulation F does not contain EDTA.

Formulation E Formulation F Component Concentration (% w/v) MAPDA 0.00050.0005 AMP-95 0.45 0.45 Boric Acid 0.6 0.6 Polyquaternium-1 0.001 0.001Sodium Citrate 0.65 0.65 Sodium Chloride 0.1 0.1 Sorbitol 1.2 1.2Tetronic 1304 0.05 0.05 Disodium EDTA 0.05 — NaOH/HCl pH 7.8 pH 7.8Purified Water QS QS

The anti-microbial activity of the above compositions against P.aeruginosa, S. marcescens, S. aureus, and C. albicans was evaluatedusing a protocol similar to that of Example 1, above. The log reductiondata is illustrated in Table 5, below:

TABLE 5 Microorganism Time (Hrs) Formulation E Formulation F P.aeruginosa 6 4.7 4.7 ATCC 9027 24 6.0 6.0 S. marcescens 6 3.2 3.3 ATCC13880 24 5.1 4.9 S. aureus 6 3.9 3.6 ATCC 6538 24 4.9 6.1 C. albicans 61.1 1.4 ATCC 10231 24 4.3 5.1 Note: Underlined number indicates nosurvivors

EXAMPLE 6

The following composition is an example of a multi-purpose compositionuseful for cleaning, rinsing, disinfecting and conditioning Rigid GasPermeable (RGP) lenses:

Component Amount Hydroxy propyl methyl cellulose 0.4% Tetronic 1304 0.5%Boric Acid 0.6% Sorbitol 1.2% Disodium Edetate 0.01% AMP-95 0.4%Propylene glycol 0.5% Polyquaternium-1 0.0005% NaOH/HCl pH 7.6 Purifiedwater QS

The anti-microbial activity of the above composition against against S.marcescens, S. aureus, and C. albicans was evaluated using a protocolsimilar to that of Example 1, above.

The log reduction data is illustrated in Table 6, below:

TABLE 6 Log₁₀ Reduction Microorganism Time of Survivors C. albicans 43.6 6 4.1 24 5.3 S. marcescens 4 3.6 6 2.6 24 5.5 S. aureus 4 5.1 6 4.824 6.1 Note: Underlined number indicates no survivors

EXAMPLE 7

The following is an example of a desinfecting composition useful forsoft hydrophilic lenses.

Component Amount Boric Acid 0.1% Sorbitol 0.2% AMP-95 0.07% Propyleneglycol 1.4% DS EDTA 0.01% Polyquaternium-1 0.0001% NaOH/HCl pH 7.6Purified water QS

The anti-microbial activity of the above composition against against S.marcescens, S. aureus, and C. albicans was evaluated using a protocolsimilar to that of Example 1, above.

The log reduction data is illustrated in Table 7, below:

TABLE 7 Log₁₀ Reduction Microorganism Time of Survivors C. albicans 61.5 24 3.0 S. marcescens 6 4.6 24 6.2 S. aureus 6 2.7 24 5.1 Note:Underlined number indicates no survivors

I claim:
 1. A method of enhancing the anti-microbial activity of anophthalmic composition containing a borate compound which comprisesadding to the composition an effective amount of a low molecular weightamino alcohol, wherein the amino alcohol has a molecular weight of from60 to 200 grams/mole.
 2. A method according to claim 1, wherein thecomposition further comprises a borate/polyol buffer system.
 3. A methodaccording to claim 1 or 2, wherein the amino alcohol is selected fromthe group consisting of 2-amino-2-methyl-1-propanol (AMP),2-dimethylamino-methyl-1-propanediol (DMAMP),2-amino-2-ethyl-1,3-propanediol (AEPD), 2-amino-2-methyl-1,3-propanediol(AMPD), 2-amino-1-butanol (AB).
 4. A method according to claim 3,wherein the composition further comprises an alkylamine.
 5. A sterile,multi-dose ophthalmic composition comprising an amount of a lowmolecular weight amino alcohol effective to enhance the anti-microbialactivity of a borate containing composition, wherein the amino alcoholhas a molecular weight of from 60 to 200 grams/mole.
 6. A compositionaccording to claim 5, wherein the composition is adapted for thetreatment of contact lenses.
 7. A composition according to claim 6,wherein the composition further comprises a borate/polyol buffer system.8. A composition according to claim 5, wherein the amino alcohol isselected from the group consisting of 2-amino-2-methyl-1-propanol (AMP),2-dimethylamino-methyl-1-propanediol (DMAMP), 2-amino-2-ethyl-1,3-propanediol (AEPD), 2-amino-2-methyl-1,3-propanediol (AMPD),2-amino-1-butanol (AB).
 9. A composition according to claim 5, 6, 7 or8, further comprising an alkylamine.
 10. A composition according toclaim 9, wherein the alkylamine is an amidoamine.
 11. A compositionaccording to claim 5 or 6, wherein the composition is a multi-purposesolution for treating contact lenses and comprises polyquatemium-1,boric acid, sorbitol, sodium chloride, sodium citrate, a nonionicsurfactant, disodium edetate, sodium hydroxide, hydrochloric acid,purified water, 2-amino 2-methyl propanol and MAPDA.
 12. A compositionaccording to claim 11, wherein the composition comprises: about 0.001%w/v of polyquaternium-1; about 0.6% w/v of boric acid; about 1.2% w/v ofsorbitol; about 0.65% w/v of sodium citrate; about 0.1% w/v of sodiumchloride; about 0.05% w/v of a nonionic surfactant about 0.05% w/v ofdisodium edetate; about 0.45% of w/v of AMP-95; about 0.0005% w/v ofMAPDA; and wherein the composition is adjusted to pH 7.8 with sodiumhydroxide and hydrochloric acid.